Alfredo De Rosa

Temporomandibular disorders (TMDs) are heterogeneous musculoskeletal conditions frequently characterized by pain, impaired mandibular function, and reduced quality of life. Botulinum neurotoxin type A (BoNT-A) has emerged as a potential therapeutic option, particularly for persistent myogenous TMDs associated with masticatory muscle hyperactivity. This narrative review critically examines the mechanisms of action, current clinical evidence, therapeutic applications, and safety profile of BoNT-A in TMD management. Available evidence suggests that BoNT-A can reliably reduce masticatory muscle activity and may provide pain relief in selected patients with refractory myogenous TMDs; however, its superiority over placebo or established conservative treatments remains inconsistent. Considerable heterogeneity in patient selection, injected muscles, dosing regimens, injection techniques, and outcome assessment currently prevents the definition of standardized treatment protocols. Although short-term adverse events are generally mild and transient, repeated injections may induce muscle atrophy, reduced bite force, and potentially mandibular skeletal changes, whose long-term clinical relevance remains uncertain. Therefore, BoNT-A should not be considered a first-line treatment but rather a carefully selected adjunct within a multimodal rehabilitation strategy after appropriate conservative management has failed. Future phenotype-stratified comparative trials with standardized protocols and long-term structural safety outcomes are warranted.

Background and Objectives: Burning Mouth Syndrome (BMS) remains a challenging condition to manage, as current treatments show variable efficacy and are often limited by tolerability, particularly in older and medically complex patients. This has prompted interest in topical neuromodulatory strategies targeting peripheral mechanisms while minimizing systemic exposure, with topical pregabalin emerging as a potential option. Materials and Methods: In this prospective longitudinal real-world study, 100 patients with BMS treated at a tertiary referral center received topical pregabalin as an off-label intraoral swish-and-spit solution. Patients were assessed at baseline and after 3 months using validated measures of pain intensity (VAS), qualitative pain perception (SF-MPQ), anxiety (HAM-A), depression (HAM-D), sleep quality (PSQI, ESS), and global clinical severity (CGI-S). Results: After 3 months, median VAS decreased from 8 (IQR 7–9) to 5 (IQR 4–6) and SF-MPQ from 10 (IQR 7–17) to 6.5 (IQR 4–10) (both p < 0.001), with concurrent improvements in anxiety, depressive symptoms, and clinical severity. Overall, 46% of patients achieved ≥30% pain reduction, while 73% and 16% reached ≥20% and ≥50% reductions, respectively. Higher baseline pain predicted greater improvement. No serious adverse events were reported. Conclusions: These findings suggest that topical pregabalin may represent a safe and potentially effective option for BMS, although controlled studies are required to confirm its efficacy.

Dysregulated microRNA (miR) expression has emerged as a potential prognostic tool in head and neck squamous cell carcinoma (HNSCC), but the clinical value of miR-34a remains unclear. This systematic review, meta-analysis, and trial sequential analysis (TSA) evaluated the association between tumor tissue miR-34a expression and survival outcomes in HNSCC. Following a protocol registered in PROSPERO (n. CRD420251238772), PubMed/MEDLINE, Scopus, ScienceDirect, CENTRAL, Google Scholar, and grey literature sources were searched for studies reporting overall survival (OS) or disease-free survival (DFS) stratified by miR-34a expression in HNSCC or its subsites. Hazard ratios (HRs) were extracted directly or reconstructed from Kaplan–Meier (KM) curves using the Tierney method, supported by a dedicated Python application (KM2HR). Four retrospective studies, corresponding to six study/site-specific cohorts and 318 patients, met the inclusion criteria. For OS (four cohorts), the fixed-effects model yielded a pooled HR of 2.25 (95% CI 1.48–3.41) for low versus high miR-34a expression, indicating worse survival in the low-expression group. However, the random-effects model attenuated the association (HR 1.32, 95% CI 0.32–5.54), with substantial heterogeneity (I² ≈ 77%). For DFS (two studies), the fixed-effects model suggested poorer outcomes with low miR-34a (HR 2.92, 95% CI 1.24–6.88), whereas the random-effects model reversed the direction of effect with extremely wide confidence intervals (HR 0.19, 95% CI ≈ 0.00–129.34; I² = 91%). TSA for OS (accrued information size 225 patients; estimated power ≈66%) crossed the monitoring boundary but did not reach the a priori information size, supporting only a tentative signal. A bioinformatic exploration of the TCGA HNSCC cohort (n = 522) showed a non-significant trend towards worse OS with low miR-34a (HR 1.24, 95% CI 0.93–1.65) and was excluded from pooling. Overall, low tumor miR-34a expression appears to be associated with poorer OS, but the evidence is limited by retrospective design, small sample size, and marked heterogeneity. miR-34a is a promising biomarker for prognostic stratification in HNSCC, yet larger, prospective, site-specific studies with standardized assays, pre-defined cut-offs, and appropriate adjustment for HPV status and clinical covariates are required before clinical implementation can be recommended.

Polyphenols are a diverse class of bioactive phytochemicals increasingly recognized for their ability to modulate human physiology through extensive interactions with the gut microbiota. This review provides a comprehensive and updated synthesis of the bidirectional polyphenol–microbiota relationship, emphasizing how dietary polyphenols reshape microbial community structure while intestinal microorganisms metabolize polyphenols into smaller, more bioavailable derivatives. These microbial metabolites—such as urolithins, phenolic acids, and dihydroresveratrol—exert amplified biological activities compared to their parent molecules, acting on key molecular pathways linked to oxidative stress, inflammation, energy homeostasis, and metabolic regulation. Through integration of mechanistic studies, multi-omics analyses, and emerging clinical evidence, this review outlines the potential of the polyphenol–microbiota–metabolite axis as a target for precision nutrition and microbiota-informed therapeutic interventions. The manuscript highlights ongoing challenges, including inter-individual variability in polyphenol metabolism, and proposes future research directions to advance the field of personalized nutrition.